Polymeric hydrogel as a vitreous substitute: current research, challenges, and future directions

Abstract

Vitreoretinal surgery is an essential approach to treat proliferative diabetic vitreopathy, retinal detachment, retinal tear, ocular trauma, and macular holes. The removal of the natural vitreous and the replacement with substitutes are critical steps for retina reattachment. Vitreous substitutes including silicone oil (SiO), air, sulfur hexafluoride (SF6), and perfluoropropane (C3F8), have been widely applied in clinical practice. However, these substitutes are reported to cause complications such as emulsification, high intraocular pressure, and lens opacification. Polymeric hydrogels are a kind of material with favorable physical, mechanical properties, and adaptable biocompatibility, thus being highly expected to be ideal vitreous substitutes. Despite years of research, very few polymeric hydrogels can be applied practically in the vitreous cavity. In this review, we focus on the development of polymeric natural-based hydrogels and synthetic hydrogels. Particularly, we pay attention to recent advances in the novel stimuli-response and self-assembly supramolecular hydrogels. Characterized by easy injectability and long residence time, this kind of hydrogel becomes the potentially promising candidates for ideal vitreous substitutes. Finally, we evaluate the current challenges and provide the future directions of vitreous substitutes.

Long-Term Biocompatibility of a Highly Viscously Thiol-Modified Cross-Linked Hyaluronate as a Novel Vitreous Body Substitute

“…Despite many years of research, very few polymeric hydrogels can be applied practically in the vitreous cavity yet, due to either a short intravitreal half-life or inflammatory or even toxic effects at the retina and in the vitreous cavity ( Nakagawa et al, 1997 ; Suri and Banerjee, 2006 ; Wang et al, 2021 ). Although it seemed obvious to develop VBS based on native hyaluronate (HA), previous studies could only show a very short half-life of less than 14 days ( Nakagawa et al, 1997 ) of non-cross-linked HA in the vitreous cavity and an increase in IOP due to intensive swelling of the hydrogel ( Pruett et al, 1979 ).…”

“…Therefore, there is great demand to develop an ideal vitreous endotamponade that mimics the physiological properties of a natural vitreous body to improve therapeutic efficacy and safety. Recent tamponade strategies aim at hydrophilic, polymeric hydrogel-based systems due to their favorable physical and mechanical properties such as high water content, high optical transparency, suitable refractive indices, viscosity, swelling pressure, adjustable rheological properties, and adaptable biocompatibility ( Schulz et al, 2020 ; Lin et al, 2021 ; Schulz et al, 2021 ; Wang et al, 2021 ). The tamponade effect of a hydrogel is exerted by the viscosity and swelling pressure, the latter via the high water-binding property; therefore, it seems logical to develop hydrogels based on hyaluronic acid, as this is one of the main components of the natural vitreous body ( Nakagawa et al, 1997 ; Schramm et al, 2012 ).…”

Risk Factors and Management of Intraocular Pressure Elevation After Vitrectomy Combined with Silicone Oil Tamponade

“…Hydrogels have emerged as a potential alternative, representing a class of hydrophilic polymers with desirable attributes such as transparency, biocompatibility, and viscoelastic properties similar to that of the vitreous humor, thus capable of emulating its biological functions. [87][88][89] Notably, smart hydrogels have garnered attention for their ability to respond to environmental and external physical stimuli. 90 However, these fillers have the potential to elicit an immune response and induce inflammation.…”

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment

“…Hydrogels can play a vital role in the development of nanotechnologies for the delivery of drugs to the eye. Regarding posterior segment delivery, polymeric natural-based hydrogels and synthetic hydrogels are characterized by easy injectability and long residence times, thus potentially promising candidates for ideal vitreous substitutes [ 200 ]. It has been demonstrated that polysaccharide crosslinked hydrogels showed sustained release of bevacizumab for three days with a low initial burst, while thermosensitive hydrogels exhibited sustained release of bevacizumab for 18 days [ 201 ].…”